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Protein

Dual specificity mitogen-activated protein kinase kinase 7

Gene

Map2k7

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K4/MKK4, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4/MKK4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The monophosphorylation of JNKs on the Thr residue is sufficient to increase JNK activity indicating that MAP2K7/MKK7 is important to trigger JNK activity, while the additional phosphorylation of the Tyr residue by MAP2K4/MKK4 ensures optimal JNK activation. Has a specific role in JNK signal transduction pathway activated by proinflammatory cytokines. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis.1 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.1 Publication

Cofactori

Mg2+1 Publication

Enzyme regulationi

Activated by phosphorylation by specific MAP kinase kinase kinases such as MAP3K1/MEKK1, MAP3K3/MEKK3, MAP3K11/MLK3 and MAP3K12/DLK.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei149 – 1491ATPPROSITE-ProRule annotationBy similarity
Active sitei243 – 2431Proton acceptorPROSITE-ProRule annotationBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi126 – 1349ATPPROSITE-ProRule annotationBy similarity

GO - Molecular functioni

  • ATP binding Source: RGD
  • JUN kinase kinase activity Source: RGD
  • magnesium ion binding Source: UniProtKB
  • MAP kinase kinase activity Source: UniProtKB
  • mitogen-activated protein kinase kinase kinase binding Source: RGD
  • protein C-terminus binding Source: RGD
  • protein serine/threonine kinase activity Source: UniProtKB-KW
  • protein tyrosine kinase activity Source: UniProtKB-KW

GO - Biological processi

  • activation of JUN kinase activity Source: RGD
  • apoptotic process Source: UniProtKB-KW
  • cellular response to sorbitol Source: RGD
  • JNK cascade Source: RGD
  • positive regulation of neuron apoptotic process Source: RGD
  • positive regulation of protein phosphorylation Source: RGD
  • protein phosphorylation Source: RGD
  • response to stress Source: UniProtKB
  • stress-activated MAPK cascade Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase, Tyrosine-protein kinase

Keywords - Biological processi

Apoptosis, Stress response

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-RNO-2559580. Oxidative Stress Induced Senescence.
R-RNO-2871796. FCERI mediated MAPK activation.
R-RNO-450321. JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.

Names & Taxonomyi

Protein namesi
Recommended name:
Dual specificity mitogen-activated protein kinase kinase 7 (EC:2.7.12.2)
Short name:
MAP kinase kinase 7
Short name:
MAPKK 7
Alternative name(s):
JNK-activating kinase 2
MAPK/ERK kinase 7
Short name:
MEK 7
c-Jun N-terminal kinase kinase 2
Short name:
JNK kinase 2
Short name:
JNKK 2
Gene namesi
Name:Map2k7Imported
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 12

Organism-specific databases

RGDi1560043. Map2k7.

Subcellular locationi

  • Nucleus By similarity
  • Cytoplasm By similarity

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: RGD
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedBy similarity
Chaini2 – 419418Dual specificity mitogen-activated protein kinase kinase 7PRO_0000271407Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanineBy similarity
Modified residuei271 – 2711Phosphoserine; by MAP3KBy similarity
Modified residuei275 – 2751Phosphothreonine; by MAP3KBy similarity

Post-translational modificationi

Activated by phosphorylation on Ser-271 and Thr-275 by MAP kinase kinase kinases (MAP3Ks).1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei44 – 452Cleavage; by anthrax lethal factorBy similarity
Sitei76 – 772Cleavage; by anthrax lethal factorBy similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiQ4KSH7.

Expressioni

Gene expression databases

ExpressionAtlasiQ4KSH7. baseline.

Interactioni

Subunit structurei

Interacts with VRK2 (By similarity). Interacts (via its D domain) with its substrates MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. Interacts (via its DVD domain) with MAP3Ks activators like MAP3K5/ASK1 and MAP3K1/MEKK1. Interacts with MAPK8IP1/JIP1, MAPK8IP2/JIP2 and MAPK8IP3/JIP3 scaffold proteins. Interacts with RASSF7, the interaction promotes phosphorylation (By similarity).By similarity

GO - Molecular functioni

  • mitogen-activated protein kinase kinase kinase binding Source: RGD
  • protein C-terminus binding Source: RGD

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000058535.

Structurei

3D structure databases

ProteinModelPortaliQ4KSH7.
SMRiQ4KSH7. Positions 103-402.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini120 – 380261Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni37 – 5721D DomainBy similarityAdd
BLAST
Regioni377 – 40024DVD domainBy similarityAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili2 – 3029Sequence analysisAdd
BLAST

Domaini

The DVD domain (residues 377-400) contains a conserved docking site and is found in the mammalian MAP kinase kinases (MAP2Ks). The DVD sites bind to their specific upstream MAP kinase kinase kinases (MAP3Ks) and are essential for activation.
The D domain (residues 37-57) contains a conserved docking site and is required for the binding to MAPK substrates.

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG0983. Eukaryota.
ENOG410XTNQ. LUCA.
GeneTreeiENSGT00760000119199.
HOGENOMiHOG000234206.
HOVERGENiHBG108518.
InParanoidiQ4KSH7.
KOiK04431.
OMAiHPVIVIT.
OrthoDBiEOG7J9VPW.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q4KSH7-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAASSLEQKL SRLEAKLKQE NREARRRIDL NLDISPQRPR PTLQLPLAND
60 70 80 90 100
GGSRSPSSES SPQHPTPPSR PRHMLGLPST LFTPRSMESI EIDQKLQEIM
110 120 130 140 150
KQTGYLTIGG QRYQAEINDL ENLGEMGSGT CGQVWKMRFR KTGHIIAVKQ
160 170 180 190 200
MRRSGNKEEN KRILMDLDVV LKSHDCPYIV QCFGTFITNT DVFIAMELMG
210 220 230 240 250
TCAEKLKKRM QGPIPERILG KMTVAIVKAL YYLKEKHGVI HRDVKPSNIL
260 270 280 290 300
LDERGQIKLC DFGISGRLVD SKAKTRSAGC AAYMAPERID PPDPTKPDYD
310 320 330 340 350
IRADVWSLGI SLVELATGQF PYKNCKTDFE VLTKVLQEEP PLLPGHMGFS
360 370 380 390 400
GDFQSFVKDC LTKDHRKRPK YNKLLEHSFI KHYETLEVDV ASWFKDVMAK
410
TESPRTSGVL SQHHLPFFR
Length:419
Mass (Da):47,536
Last modified:August 2, 2005 - v1
Checksum:i60405BF7111E294B
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY879265 mRNA. Translation: AAX61178.1.
RefSeqiNP_001020596.1. NM_001025425.1.
UniGeneiRn.162081.

Genome annotation databases

EnsembliENSRNOT00000061821; ENSRNOP00000058535; ENSRNOG00000001047.
GeneIDi363855.
KEGGirno:363855.
UCSCiRGD:1560043. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY879265 mRNA. Translation: AAX61178.1.
RefSeqiNP_001020596.1. NM_001025425.1.
UniGeneiRn.162081.

3D structure databases

ProteinModelPortaliQ4KSH7.
SMRiQ4KSH7. Positions 103-402.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000058535.

Proteomic databases

PaxDbiQ4KSH7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000061821; ENSRNOP00000058535; ENSRNOG00000001047.
GeneIDi363855.
KEGGirno:363855.
UCSCiRGD:1560043. rat.

Organism-specific databases

CTDi5609.
RGDi1560043. Map2k7.

Phylogenomic databases

eggNOGiKOG0983. Eukaryota.
ENOG410XTNQ. LUCA.
GeneTreeiENSGT00760000119199.
HOGENOMiHOG000234206.
HOVERGENiHBG108518.
InParanoidiQ4KSH7.
KOiK04431.
OMAiHPVIVIT.
OrthoDBiEOG7J9VPW.

Enzyme and pathway databases

ReactomeiR-RNO-2559580. Oxidative Stress Induced Senescence.
R-RNO-2871796. FCERI mediated MAPK activation.
R-RNO-450321. JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.

Miscellaneous databases

PROiQ4KSH7.

Gene expression databases

ExpressionAtlasiQ4KSH7. baseline.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. Itoh T., Horiuchi M., Itoh A.
    Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Sprague-DawleyImported.
  2. "Stress- and cell type-dependent regulation of transfected c-Jun N-terminal kinase and mitogen-activated protein kinase kinase isoforms."
    Butterfield L., Zentrich E., Beekman A., Heasley L.E.
    Biochem. J. 338:681-686(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  3. "Delayed activation and regulation of MKK7 in hippocampal CA1 region following global cerebral ischemia in rats."
    Zhang Q., Tian H., Fu X., Zhang G.
    Life Sci. 74:37-45(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION, INTERACTION WITH MAPK8/JNK1; MAPK9/JNK2; MAPK10/JNK3; MAP3K11/MLK3 AND MAP3K5/ASK1.
  4. "Differential regulation and properties of MAPKs."
    Raman M., Chen W., Cobb M.H.
    Oncogene 26:3100-3112(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON ENZYME REGULATION.
  5. "Diverse physiological functions of MKK4 and MKK7 during early embryogenesis."
    Asaoka Y., Nishina H.
    J. Biochem. 148:393-401(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON FUNCTION.
  6. "The bottleneck of JNK signaling: molecular and functional characteristics of MKK4 and MKK7."
    Haeusgen W., Herdegen T., Waetzig V.
    Eur. J. Cell Biol. 90:536-544(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON REGULATION, REVIEW ON FUNCTION.

Entry informationi

Entry nameiMP2K7_RAT
AccessioniPrimary (citable) accession number: Q4KSH7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 9, 2007
Last sequence update: August 2, 2005
Last modified: June 8, 2016
This is version 92 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.